Amyl nitrite (C5H11ONO) is a known vasodilator and expands blood vessel to lower blood pressure. It is therefore employed to treat heart disease and angina. In addition, amyl nitrite is used as an antidote for cyanide poisoning where it acts as an oxidant to induce the formation of methemoglobin which in turn can attenuate cyanide as cyanomethemoglobin. The alkyl group is generally unreactive and the chemical and biological properties are primarily due to the nitrite (ONO) group.
U.S. Pat. No. 3,106,511 relates to medicament compositions containing amyl nitrite and to their preparation and use. U.S. Pat. No. 4,309,303 relates to a method of stabilizing liquid alkyl nitrites by adding ethyl hydroxyethyl cellulose, calcium silicate and mixtures thereof and mixing to produce solid state compositions and to stabilize compositions thereof. U.S. Patent Publication No. 2003/0149292 relates to the continuous synthesis of alkyl nitrites by reacting an alcohol with an inorganic nitrite in an acidic medium.
However, amyl nitrite's utility as a field antidote treatment remains limited by its drug product stability characteristics (presently 2 year storage at 2-8° C. and limited storage at 25° C.). It is also known that amyl nitrite is unstable unless protected for oxygen and light. Thus, even with stabilization it cannot be left unprotected for relatively long periods of time.
In addition, amyl nitrite is administered by nasal inhalation, which makes it difficult to determine dose level and the amount of amyl nitrite that is delivered (as measured by blood methemoglobin concentration) is relatively low. Additionally, due to unknown dose delivery, there has been no dose to efficacy or dose to safety relationship established.
It is also useful to note that amyl nitrite is a relatively low viscosity and volatile fluid with a boiling point of 97-99° C. As noted, it is typically employed in drug form by inhalation of vapors of the liquid. Accordingly, the relative high volatility will separately reduce the efficacy of a dose through evaporation away from the target zone or uncontrolled release.